An efficient biomimetic Fe-catalyzed epoxidation of olefins using hydrogen peroxide

Article abstract of DOI:10.1039/b612048b

A new, environmentally benign and practical epoxidation method was developed using inexpensive and efficient Fe catalysts. FeCl₃· 6H₂O in combination with commercially available pyridine-2,6- dicarboxylic acid and amines showed excellent reactivity and selectivity towards aromatic olefins and moderate reactivity towards 1,3-cyclooctadiene utilizing H₂O₂ as the terminal oxidant. The Royal Society of Chemistry.

Full text of DOI:10.1039/b612048b

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An efficient biomimetic Fe-catalyzed epoxidation of olefins using
hydrogen peroxide{
Gopinathan Anilkumar,a Bianca Bitterlich,a Feyissa Gadissa Gelalcha,a Man Kin Tseab and
Matthias Beller*ab
Received (in Cambridge, UK) 22nd August 2006, Accepted 28th September 2006
First published as an Advance Article on the web 27th October 2006
DOI: 10.1039/b612048b
our work on Fe catalysts, we tried to extrapolate our previously
developed Ru reaction protocols15–18 with Fe. Not surprisingly,
initial attempts with pre-made Fe complexes resulted in low yield
and selectivity. Therefore in situ generated iron complexes, which
are more easily tuned, were used for the epoxidation of trans-
stilbene at room temperature.19
A screening of different iron sources of Fe2+ and Fe3+ in the
presence of acid or base revealed that complete conversion was
observed only in the case of FeCl3?6H2O. Hence, our further
investigations focused on this iron source. While studying various
nitrogen ligands, it was observed that simply pyridine-2,6-
dicarboxylic acid (H2pydic) is sufficient to form an active Fe
epoxidation catalyst! Advantageously, the in situ formation of the
active complex with H2pydic and Fe occurs at rt. The combination
of FeCl3?6H2O, H2pydic, and an organic base, such as
benzylamine, 4-methylimidazole and pyrrolidine, leads to an active
and highly selective epoxidation catalyst (see ESI{).
Unlike the corresponding Ru complexes, the use of disodium
pyridine-2,6-dicarboxylate or using H2pydic with 10 mol% of
inorganic base was not effective in the case of Fe. To our delight,
the addition of organic bases, such as benzylamine, 4-methylimi-
dazole and pyrrolidine, gave full conversion and almost quanti-
tative yield and selectivity. It is envisaged that one of the roles of
the base is to deprotonate the pyridine-2,6-dicarboxylic acid;
however reports on the influence of base on the stability of the
catalyst and selectivity of the oxidation are known.20 When the
NH group of imidazole was substituted with an alkyl group,
the reactivity remained. However, the reactivity dropped signifi-
cantly when 2-methylimidazole was used (12% conv., 11% yield).
In comparison with the reactivity of pyridine (56% conv., 50%
yield) and pyrrolidine (100% conv., 97% yield), this effect must be
attributed to coordination effects to some extent. This is not the
case with 4-methylimidazole, which led to full conversion with
excellent yield (97%) of trans-stilbene oxide. In order to explain the
observed ligand effects, gelicification and redissolution of the
ligand or catalyst should be considered, too. Such effects were
reported during the deprotonation of the pyridine-2,6-dicarboxylic
acid in aqueous alkaline solution due to pH dependent electrostatic
interactions and hydrogen bonding between the polar species and
water.21 We have not noticed any such process in our reactions,
obviously due to the less polar nature of tert-amyl alcohol
compared to water. Importantly, the formation of trans-stilbene
oxide was not observed when pyrrolidine, pyridine-2,6-dicar-
boxylic acid or the iron source was not used in the reaction. It is
remarkable that the epoxidation reaction is quite fast and an
optimum yield can be achieved by addition of the oxidant (H2O2)
A new, environmentally benign and practical epoxidation
method was developed using inexpensive and efficient Fe
catalysts. FeCl3?6H2O in combination with commercially
available pyridine-2,6-dicarboxylic acid and amines showed
excellent reactivity and selectivity towards aromatic olefins and
moderate reactivity towards 1,3-cyclooctadiene utilizing H2O2
as the terminal oxidant.
Nature utilizes iron-proteins such as hemoglobin, myoglobin, and
cytochrome oxygenases for vital biochemical processes such as
transport of oxygen and electron transfer reactions in plants,
animals and microorganisms.1–3 Understanding such mechanisms
may lead to new insights in biocatalysis and drug design as well as
the development of new industrial catalysts.
Following nature’s path, numerous reports on biomimetic
oxidation of olefins using metalloporphyrins are known at present;
a major problem curtailing these catalysts for use in industry is
their difficult multi-step synthesis.4 Among the various oxidation
methods, epoxidation of olefins continues to be an important field
of research in industry and academia due to the formation of two
C–O bonds in one reaction and the facile opening of the epoxide
ring to useful synthons.5
With respect to the oxidants6 commonly used, molecular
8
oxygen7 and H2O2 are the reagents of choice. The latter is more
convenient to use and produces only water as the by-product.
Thus, a combination of H2O2 with a catalytic amount of cheap
and relatively non-toxic metals such as Mn or Fe would be an ideal
system for large scale production in industry. However, the use of
H2O2 in combination with simple non-heme manganese9 or iron10
is limited, since H2O2 is well-known to decompose vigorously in
the presence of these metals.11 Consequently, iron-catalyzed
epoxidation using non-heme complexes and H2O2 are scant in
the literature.12 For example, the Jacobsen’s Fe-mep catalyst13 is
known to epoxidize aliphatic olefins in the presence of acetic
acid.14 However, to the best of our knowledge there is no Fe
catalyst known which allows for a general epoxidation under
neutral conditions.12c
In this context, we were interested in exploring the possibility of
Fe-catalyzed epoxidation using H2O2, since iron and H2O2 are
cheap, environmentally benign and reactive. As a starting point of
aLeibniz-Institut fu¨r Katalyse, Albert-Einstein Strabe 29a, Rostock,
D-18059, Germany
bCenter for Life Science Automation, Friedrich-Barnewitz-Strabe 8,
D-Rostock, 18119, Germany. E-mail: matthias.beller@catalysis.de;
Fax: +49 381-1281-5000; Tel: +49 381-1281-113
{ Electronic supplementary information (ESI) available: Base effect of Fe-
catalyzed epoxidation of trans-stilbene. See DOI: 10.1039/b612048b
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Chem. Commun., 2007, 289–291 | 289

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over a period of one hour using a syringe pump. Even an addition
of hydrogen peroxide within 5 minutes showed no decrease in
reactivity and selectivity for trans-stilbene.
the mechanism of the reaction in more detail, trans-stilbene was
subjected to epoxidation using the new protocol in the presence of
a radical scavenger (2,6-di-tert-butyl-4-methoxyphenol), which
afforded the epoxide in very low yield (,10%) suggesting a
selective radical pathway occurring as the major process in this
reaction. Although to date we have no direct structural evidence of
the active catalyst species, and discussions on the nature of the
intermediate are so far speculative,22 non-heme dioxygenases, such
as TauD,23 TfdA24 and NDO,25 which contain carboxylate and
histidine on their coordination sphere, may give us some insights.26
In conclusion, we have developed a new biomimetic, convenient
and fast epoxidation protocol using a cheap and environmentally
friendly iron source in combination with H2O2. The system
showed excellent reactivity and selectivity towards terminal and
1,2-disubstituted aromatic olefins, and moderate reactivity towards
1,3-dienes. Unlike previous procedures, our protocol is much
simpler and demands no pre-made catalyst, acetic acid or freezing
reaction temperature. Gratifyingly, all the reagents used in our
Next, different substrates were tested in these optimized reaction
conditions (Table 1). Styrene, generally known as a difficult
substrate for epoxidation, afforded excellent yield and selectivity of
styrene oxide (Table 1, entries 3–4). The reaction also performed
well for ortho- and electron donating/withdrawing substituted
styrenes (Table 1, entries 5–8). Cinnamyl acetate, cinnamyl
chloride, and cis- as well as trans-b-methyl styrene gave good to
excellent yields (Table 1, entries 9–13). In the case of a-methyl
styrene, in addition to the epoxide,
a small amount of
2-phenylpropanal was also formed, presumably by the iron-
promoted rearrangement of the epoxide via a stable benzyl
carbocation.
To further extend the scope of the reaction 1,3-cyclooctadiene
was tested. Here, the corresponding mono-epoxide is obtained in
65% yield with 84% selectivity (Table 1, entry 14). To understand
Table 1 Scope and limitations of the reaction
Entry
Substrate
Conv. (%)a,b
Yield (%)b
Selectivity (%)c
1
2
3
4
100
98d
94
97
97
96d
93
98d
99
88d
69d
78d
5
6
100
88d
97
87d
97
99d
7
8
100
100d
77
79d
77
79d
9
71
77
69
63
95
97
82
95
10
11
100
12
13
75
93
56e
64
75
69
14
77
65
84
a
Reaction conditions: in a 25 mL Schlenk tube, FeCl3?6H2O (0.025 mmol), H2pydic (0.025 mmol), tert-amyl alcohol (9 mL), pyrrolidine
(0.05 mmol), olefin (0.5 mmol) and dodecane (GC internal standard, 100 mL) were added in sequence at rt in air. To this mixture, a solution of
30% H2O2 (114 mL, 1.0 mmol) in tert-amyl alcohol (886 mL) was added over a period of 1 h (or 5 min) at rt by a syringe pump. Conversion
b
c
d
and yield were determined by GC analysis. Selectivity refers to the ratio of yield to conversion as percentage. The oxidant was added over a
period of 5 min. 19% trans-b-methylstyrene oxide was observed.
e
290 | Chem. Commun., 2007, 289–291
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D. Mandelli, Tetrahedron Lett., 2005, 46, 4563; (b) D. H. R. Barton and
B. Hu, Pure Appl. Chem., 1997, 69, 1941; (c) D. H. R. Barton and
D. K. Taylor, Pure Appl. Chem., 1996, 68, 497.
system are simple and commercially available and the reaction can
be performed at rt. To the best of our knowledge, the system
described here is the simplest and most practical iron-catalyzed
epoxidation procedure available for olefins today. Efforts are
underway in our group aimed at realizing the asymmetric version
of this reaction.
11 (a) W. Nam, R. Ho and J. S. Valentine, J. Am. Chem. Soc., 1991, 113,
7052; (b) T. G. Traylor, S. Tsuchiya, Y. S. Byun and C. Kim, J. Am.
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12 (a) For an iron(II) tpa complex (tpa = tris-(2-pyridylmethyl)amine)
catalyzed epoxidation of olefins by in situ formation of peracetic acid
from H2O2 and HOAc applied to a few substrates affording a mixture
of epoxides and diols, see: M. Fujita and L. Que, Jr., Adv. Synth. Catal.,
2004, 346, 190. (b) for epoxidation of cyclooctene by H2O2 catalyzed by
iron complexes yielding a mixture of epoxide and diol, see: K. Chen,
M. Costas, J. Kim, A. T. Tipton and L. Que, Jr., J. Am. Chem. Soc.,
2002, 124, 3026. (c) for oxidation of olefins by activation of H2O2 with
anhydrous FeCl3 yielding a mixture of epoxide, dimer and aldehydes,
see: H. Sugimoto and D. T. Sawyer, J. Org. Chem., 1985, 50, 1786. (d)
H. Sugimoto, L. Spencer and D. T. Sawyer, Proc. Natl. Acad. Sci.
U. S. A., 1987, 84, 1731.
13 mep = N,N9-dimethyl-N,N9-bis(2-pyridylmethyl)-ethane 1,2-diamine,
see: M. C. White, A. G. Doyle and E. N. Jacobsen, J. Am. Chem.
Soc., 2001, 123, 7194.
14 Stack’s Fe-phenanthroline system also epoxidizes olefins with
CH3CO3H, see: G. Dubois, A. Murphy and T. D. P. Stack,
Org. Lett., 2003, 5, 2469.
15 (a) M. K. Tse, S. Bhor, M. Klawonn, C. Do¨bler and M. Beller,
Tetrahedron Lett., 2003, 44, 7479; (b) S. Bhor, M. K. Tse, M. Klawonn,
C. Do¨bler, W. Ma¨gerlein and M. Beller, Adv. Synth. Catal., 2004, 346,
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and M. Beller, Angew. Chem., 2004, 116, 5367 (Angew. Chem., Int. Ed.,
2004, 43, 5255).
We thank the State of Mecklenburg-Western Pommerania, the
Federal Ministry of Education and Research (BMBF) and the
Deutsche Forschungsgemeinschaft (SPP 1118 and Leibniz-prize)
for financial support. Dr D. Michalik, Mrs C. Mewes, Mrs A.
Lehmann, Mrs C. Fisher and Mrs S. Buchholz (LIKAT) are
acknowledged for their technical and analytical support.
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Chem. Commun., 2007, 289–291 | 291